In recent years much research work has been done in development of systems for use in release of active chemicals, over a period of time, into host systems. Such host systems include the human body, soil systems, aquatic bodies; the active ingredients for each such host could be, e.g., antibiotics, insecticides, or herbicides.
Much of the work has been directed towards the development of polymer matrices that will decompose harmlessly in the host system. A series of patents issued to Schmitt et al (e.g. U.S. Pat. No. 3,736,646 which lists a number of other such patents) describes a considerable amount of work related to polymers of polylactic and polyglycolic acid in various applications. Usually the polymer is used as an absorbable suture or bone pin - but use of such polymers as a matrix for pharmaceutical products such as steroids is also disclosed generally. In addition, lipid and protein vehicles have been used as release-moderating matrices relying on enzymatically-accentuated release (U.S. Pat. No. 3,493,652). U.S. Pat. No. 3,279,996 discloses diffusion of drug through polymer walls and describes the rate of release of drug molecules from the implant as a function of the degree of solubility of the drug in silicone rubber.
In general the prior art has been directed toward (1) obtaining polymers which are decomposable within the host system into physiologically-tolerable products which can be disposed of by the metabolism of the host system (2) to attempting achieve a predictable release rate from such products during their effective medication period. Usually the investigators have modified the release rate by (1) using concentration gradients of the active agent in the matrix, (2) selecting shape and size of the articles or (3) limiting diffusion rates by use of semipermeable barrier layers. Scuh investigators have largely accepted the compositions which are most readily obtained by combining matrix and active ingredient.
Applicants, as will be described below, have not followed this procedure but have discovered that significant advances in predictability and control of release rates can be made by careful control of the interaction between matrix and the active agent.